Larimar Therapeutics, Inc. · NASDAQ:LRMR
Larimar Therapeutics — Investor Presentation (July 2021)
36 slides from Larimar Therapeutics's investor presentation, Jul 1, 2021
Slide 1: Larimar Therapeutics Corporate Presentation July 2021
Exhibit 99.1 Larimar Therapeutics Corporate Presentation July 2021 1Exhibit 99.1 Larimar Therapeutics Corporate Presentation July 2021 1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements that are based on the beliefs and assumptions of Larimar Therapeutics, Inc. (the “Company”) and on information currently available to management. All statements contained in this presentation other than statements of hi
Slide 3: Investment Highlights
Investment Highlights Clinical-stage biotechnology company with a novel protein replacement therapy platform Focused on addressing unmet needs in Friedreich's ataxia (FA) and other complex rare diseases based on a platform technology backed by a strong intellectual property portfolio Lead candidate:
Slide 4: CTI-1601 is Designed to Deliver Additional Frataxin (FXN)
CTI-1601 is Designed to Deliver Additional Frataxin (FXN) CTI-1601 Maintains the Cleavage Site Between the MTS and Mature Human FXN STRUCTURE OF CTI-1601 STRUCTURE OF ENDOGENOUS FXN Mitochondrial Targeting Mature Mitochondrial Targeting Mature Sequence (MTS) Human FXN Sequence (MTS) Human FXN Cleava
Slide 5: Platform Technology is Supported by a Strong IP Portfolio
Platform Technology is Supported by a Strong IP Portfolio Pending CTI-1601 patent application, if issued, extends IP into 2040 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 TAT-MTS-FXN Composition of Matter (broad coverage of CTI-1601) Expiration US 9,045,552 (Exclusive license from Wake Forest)
Slide 6: Friedreich's Ataxia (FA) Rare and Progressive Disease
Friedreich’s Ataxia (FA) Rare and Progressive Disease Caused by genetic defect resulting in low levels of frataxin • Patients with FA only produce ~20-40% of normal frataxin levels depending 1 on the tissue, sampling technique, and assay considered • Affects ~5,000 patients in the U.S. & ~20,000 pat
Slide 7: Strong Relationship with FARA
Strong Relationship with FARA Company has strong relationship with Friedreich’s Ataxia Research Alliance (FARA) • National, non-profit organization dedicated to the pursuit of scientific research leading to treatments and a cure for FA FARA provides industry with several key items • Assistance with
Slide 8: Executive Summary of Phase 1 POC Data
Executive Summary of Phase 1 POC Data CTI-1601 appears to be generally well tolerated at doses up to 100 mg Safety administered daily for 13 days Daily dosing of CTI-1601 resulted in dose-dependent increases in FXN levels from Pharmacodynamics baseline compared to placebo controls in all evaluated t
Slide 9: CTI-1601: Phase 1 Clinical Program in Patients with FA
CTI-1601: Phase 1 Clinical Program in Patients with FA Program consisted of double-blind, placebo controlled single- and multiple-ascending dose trials Phase 1 Development Plan • Two double-blind, placebo-controlled dosing trials in patients with FA • Patient dosing began December 2019 • Safety Revi
Slide 10: MAD Trial Patient Enrollment
MAD Trial Patient Enrollment 16 out of 28 patients who participated in the SAD trial enrolled in the MAD trial MAD Trial Patient Enrollment (n=27) Parameter Statistic Overall Participated in SAD trial? Yes n (%) 16 (59%) No n (%) 11 (41%) Cohort 1 (25 mg) Active vs. Placebo Active n (%) 6 (75%) Plac
Slide 11: Multiple Ascending Dose Study Design
Multiple Ascending Dose Study Design Treatment Schedules for Each Cohort Cohort 1 (25 mg; n = 8) Cohort 2 (50 mg; n = 9) Cohort 3 (100 mg n = 10) 13-day Treatment Period 13-day Treatment Period 13-day Treatment Period 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8
Slide 12: Dose Dependent Increases in FXN Levels Observed in Buccal Cells
Dose Dependent Increases in FXN Levels Observed in Buccal Cells Daily SC injections of 100 mg CTI-1601 resulted in an ~2.5 fold increase in FXN levels from baseline FXN* Levels By Dose Group FXN* Change from Baseline By Dose Group (Buccal Cells) (Buccal Cells) Baseline Day 4/7 Day 13 Day 4/7 Day 13
Slide 13: Dose Dependent Increases in FXN Levels Observed in Skin
Dose Dependent Increases in FXN Levels Observed in Skin Daily SC injections of 100 mg CTI-1601 resulted in an ~3 fold increase in FXN levels from baseline FXN* Levels By Dose Group FXN* Change from Baseline By Dose Group (Skin Biopsies) (Skin Biopsies) Baseline Day 13 Day 13 th th *FXN levels measur
Slide 14: Dose Dependent Increases in FXN Levels Observed in Platelets
Dose Dependent Increases in FXN Levels Observed in Platelets with Daily Dosing Daily SC injections of CTI-1601 resulted in increases in FXN levels from baseline compared to placebo FXN* Levels By Dose Group FXN* Change from Baseline By Dose Group (Platelets) (Platelets) Baseline Day 4/7 Day 13 Day 4
Slide 15: Increases in FXN Correlated with Increasing CTI-1601 Dose
Increases in FXN Correlated with Increasing CTI-1601 Dose Individual patient data further supports the dose-dependent effects of CTI-1601 in all tissues studied # Buccal Cells Day 13 FXN* Skin Biopsies Day 13 FXN* Platelets Day 13 FXN* Change from Baseline Change from Baseline Change from Baseline S
Slide 16: Data Compare Favorably to FXN Levels Expected in Heterozygous Carriers
Data Compare Favorably to FXN Levels Expected in Heterozygous Carriers Achieved median FXN levels that were >60% of the median FXN levels observed in healthy controls FXN* Levels By Dose Group Benchmarking Clinical Relevance (Buccal Cells) • FXN levels in buccal cells and blood have been shown to co
Slide 17: Summary of MAD trial safety data
Summary of MAD trial safety data: Repeated SC Repeated doses (25 mg, 50 mg, and 100 mg) of CTI-1601 or placebo were administered subcutaneously. 27 patients were dosed in the trial. 26 patients injections of CTI- completed the trial. 1 patient receiving CTI-1601 in Cohort 2 (50 mg) withdrew 1601 app
Slide 18: Summary of PK Analyses
PK analyses Summary of PK Analyses CTI-1601 was quickly absorbed after subcutaneous administration support evaluating Dose-proportional increases in exposure observed with increasing doses of CTI-1601 a once-daily Mean half life of CTI-1601 in plasma was approximately 11 hours dosing regimen for CTI
Slide 19: Phase 1 Topline Data Demonstrated POC for CTI-1601 in FA
Phase 1 Topline Data Demonstrated POC for CTI-1601 in FA 1 FXN levels in buccal cells & blood have been shown to correlate with disease severity in FA patients Frataxin Pharmacokinetic Safety Data Measurements Data Repeated SC injections of CTI- Daily SC injections of CTI-1601 CTI-1601 was quickly a
Slide 20: CTI-1601 has a Significant Estimated Safety Margin
CTI-1601 has a Significant Estimated Safety Margin Based on the 90-day Cynomolgus Monkey Study Cynomolgus Monkey (28-day and 90-day studies) Sprague Dawley Rat (28-day and 90-day studies) Injection Site Observations Injection Site Observations • Some injection sites raised and firm; dose dependent •
Slide 21: Upcoming Trials and Regulatory Interactions
Upcoming Trials and Regulatory Interactions Additional analyses from the Phase 1 program planned for presentation at a scientific meeting Future Planned Trials and Regulatory Interactions Include: MAD trial in patients under 18 Global double-blind Continued interactions with FDA Jive open label exte
Slide 22: Expect to Initiate Two Additional Trials in 2H 2021/1H 2022
Expect to Initiate Two Additional Trials in 2H 2021/1H 2022 Patients from SAD, MAD, and pediatric trials are eligible to screen for the Jive open label extension trial OLE Trial SAD Trial Patients Patients eligible to enroll from Phase 1/Pediatric Dose Level: To be determined based on additional ana
Slide 23: Investment Highlights
Investment Highlights Clinical-stage biotechnology company with a novel protein replacement therapy platform Focused on addressing unmet needs in Friedreich's ataxia (FA) and other complex rare diseases based on a platform technology backed by a strong intellectual property portfolio Lead candidate:
Slide 24: Larimar Therapeutics THANK YOU
Larimar Therapeutics Corporate Presentation THANK YOU 24Larimar Therapeutics Corporate Presentation THANK YOU 24
Slide 25: Leadership Team
Leadership Team Carole Ben-Maimon, MD Michael Celano Nancy Ruiz, MD, FACP, FIDSA Jennifer Johansson, JD Mohamed Hamdani Chief Executive Officer Chief Financial Officer Chief Medical Officer VP, Regulatory Affairs & Counsel VP, Biostatistics & Data Management David Bettoun, PhD Keith E. Lynch, Jr. Jo
Slide 26: Scientific Advisory Board
Scientific Advisory Board Giovanni Manfredi, Marshall Summar, Marni J. Falk, Russell Clayton, Mark Payne, MD DO (Chairman) MD, PhD MD MD Finbar and Marianne Kenny Co-founder of Chondrial Chief of the Division of Executive Director of the Former Chief Medical Officer Professor in Clinical and Therape
Slide 27: MAD Trial Patient Demographics
MAD Trial Patient Demographics 25 mg 50 mg 100 mg All All placebo Overall Parameter Statistic CTI-1601 CTI-1601 CTI-1601 CTI-1601 (n=7) (n=27) (n=6) (n=7) (n=7) (n=20) Sex 4 ( 57.1) 3 ( 42.9) 10 ( 50.0) 15 (55.6) Male n (%) 5 (71.4) 3 ( 50.0) Female n (%) 2 (28.6) 3 ( 50.0) 3 ( 42.9) 4 ( 57.1) 10 (
Slide 28: MAD Trial Patient Disease Characteristics
MAD Trial Patient Disease Characteristics 25 mg 50 mg 100 mg All All placebo Overall Parameter Statistic CTI-1601 CTI-1601 CTI-1601 CTI-1601 (n=7) (n=27) (n=6) (n=7) (n=7) (n=20) Age at Symptom Onset 14.1 24.0 19.3 11.9 18.1 17.1 Mean SD 5.34 14.48 6.21 6.72 10.37 9.39 15.0 18.0 19.0 10.0 18.0 16.0
Slide 29: CTI-1601: Positive Mouse Model Data Support Development
CTI-1601: Positive Mouse Model Data Support Development Proof-of-Concept Demonstrated In Mouse Models of FA Cardiac Knock Out Mouse Model Studies Neurologic Knock Out Mouse Model Study (MCK-Cre FXN KO Mouse) (Pvalb-CRE FXN KO Mouse) Extended survival Prevented development of ataxic gait Demonstrated
Slide 30: CTI-1601 Extends Survival in FXN-deficient KO Mice
CTI-1601 Extends Survival in FXN-deficient KO Mice Initial Proof of Concept for FXN Replacement Therapy in Cardiac Mouse Model of FA Median Survival of MCK-Cre FXN-KO Mice • 166 days (CTI-1601) vs. 98 days (Vehicle) • CTI-1601 was administered 10 mg/kg SC every other day P=0.0001 Survival beyond veh
Slide 31: CTI-1601 Prevents Development of Ataxic Gait in Pvalb-Cre FXN-KO Mouse
CTI-1601 Pvalb-Cre FXN-KO mouse Prevents The Single dose level: 10 mg/kg CTI-1601 or vehicle given intraperitoneally three times per week Development of hFXN replacement with CTI-1601 prevents the development of ataxic gait Ataxic Gait in CTI-1601-treated mice survive longer than untreated mice KO m
Slide 32: CTI-1601 Delivers hFXN to Mitochondria in KO Mice
CTI-1601 Delivers hFXN to Mitochondria in KO Mice • hFXN concentration within mitochondria increases in a dose-dependent manner • Given subcutaneously, CTI-1601 functionally replaces hFXN in mitochondria of KO mice • Succinate dehydrogenase (SDH) activity, which is indicative of mitochondrial functi
Slide 33: CTI-1601 Prevents Left Ventricle Dilation in KO Mice
CTI-1601 Prevents Left Ventricle Dilation in KO Mice • Left ventricular (LV) volume increases in systole in untreated mice by 8 weeks (after 4 weeks of dosing with vehicle), but remains similar to wildtype when treated with CTI-1601 (10 mg/kg every other day) • CTI-1601-treated mice have similar LV
Slide 34: CTI-1601 Preserves Left Ventricle Function in KO Mice
CTI-1601 Preserves Left Ventricle Function in KO Mice • Left ventricular (LV) function drops significantly in vehicle treated mice by week 8 • CTI-1601-treated (10 mg/kg every other day) mice have similar LV as healthy controls; echocardiogram shows significant differences between vehicle and CTI-16
Slide 35: Favorable PK/PD Profile in Healthy Cynomolgus Monkeys
Favorable PK/PD Profile in Healthy Cynomolgus Monkeys Study Design (14-Days of CTI-1601 dosing) • CTI-1601 is bioavailable when given subcutaneously 6 healthy cynomolgus monkeys (3M / 3F) • Sustained levels of hFXN are found in blood cells (platelets) and peripheral Pre-dosed for 2 days with Vehicle
Slide 36: Biodistribution in Healthy Cynomolgus Monkeys
Biodistribution in Healthy Cynomolgus Monkeys Sustained levels of human FXN (hFXN) in peripheral tissues after 14 days of CTI-1601 dosing Buccal Swabs Skin Biopsies Platelets (Pre-treatment) (Pre-treatment) (Pre-treatment) Human + Monkey FXN CTI-1601 Human FXN • Treatment of monkeys with CTI-1601 re
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